Background: Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease. The diagnosis is based on a combination of the motor signs: tremor, bradykinesia, rigidity and postural abnormalities. Mild Cognitive Impairment (MCI) is common early in the disease and a large proportion of patients with PD develop dementia (PDD). Associations between motor symptoms and cognitive decline have been suggested but the results are inconclusive due to differences in the selection of participants and variables tested. Large population based studies with comprehensive neuropsychological investigation in newly diagnosed cases with PD followed prospectively are rare. The aim of this thesis was to improve characterization and understanding of cognition in PD, and to explore the relationship to motor impairment in the early phase of PD. Methods: All new patients with suspected idiopathic parkinsonism in the catchment area (142 ooo inhabitants) were examined during a period of five years and four months. Among other investigations, a comprehensive neuropsychological evaluation was carried out in 119 of 148 patients with PD together with 30 age matched healthy controls. Assessments were repeated after one three and five years. Results: Patients performed worse than healthy controls in a majority of neuropsychological tests. MCI at the time of diagnosis were found in 36% according to recently published MCI criteria. Thirty % were cognitively impaired using another definition. One fourth of the patients developed PDD within five years after diagnosis and 25 % of those with MCI at baseline reversed back to normal cognition. Age and MCI were significant predictors of dementia. Education was an independent predictor for severe cognitive dysfunction at diagnosis but did not predict PDD. Patients with MCI converting to PDD had worse performance on visuospatial function, semantic fluency, episodic memory, mental flexibility and conceptual thinking. There were no differences in cognitive performance between patients with predominant Postural and Gait Disturbances (PIGD) and the tremor dominant subtype at the baseline investigation and belonging to the PIGD subgroup at baseline did not predict PDD. Dementia converters declined more rapidly than non-converters in posture/gait function. Associations between bradykinesia and measures of executive functions and working memory were found, and between posture and gait disturbances and visuospatial function. Some of these associations were persistent after one year. Patients receiving the dopamine agonist pramipexole performed significantly worse on a measure of verbal fluency at the one year follow up. Conclusions: The differences in proportions of cognitively impaired in the different studies emphasize the value of joint criteria for PD-MCI. Even when using such criteria, a substantial proportion of patients revert back to normal function. The increase in motor disability in patients with PDD could have several different causes that need to be further investigated. Associated motor and cognitive dysfunctions could reflect common pathophysiological processes in partly shared networks. Both dopaminergic and non-dopaminergic motor and cognitive functions seems to be involved in PDD which suggests that pharmacological treatment in PD needs to go beyond the scope of dopaminergic deficiency in search for new therapies that would also be effective for non-motor symptoms. / NYPUM

Impaired attention can hinder information processing at multiple levels and may explain some aspects of the cognitive decline in aging. An inefficient inhibitory system can lead to deficits in focused attention (FA). FA deficits are observed in patients with mild cognitive impairment and Alzheimer’s disease (AD). The Stroop task was applied to functional magnetic resonance imaging (fMRI) to investigate the neural correlates of FA in cognitively normal older adults (NC), patients with amnestic MCI (aMCI) and patients with mild AD. Twenty-one NC, seven aMCI and fifteen mild AD patients performed a verbal Stroop- fMRI paradigm. Both structural and T2*-weighted functional scans were acquired. In Series 0, subjects were presented with colour words printed in black ink and were asked to read the word. In Series 1 and 2, subjects were presented with colour words printed in an incongruent ink colour. Series 1 had four blocks of the ‘Read the word’ condition followed by four blocks of the ‘Say the colour of the ink’ condition. Series 2 had eight blocks of alternating ‘Read the word’ and ‘Say the colour of the ink’ conditions. SPM5 was used to detect anatomical areas with significant signal intensity differences between the two conditions. The NC group performed significantly better in the Stroop-fMRI task than the aMCI and mild AD groups. The percentage of errors on incongruent trials was significantly lower in the NC group (2%) than the aMCI (14%) and mild AD (13%) groups. The ‘Say the colour of the ink’ minus ‘Read the word’ contrast for the NC and mild AD groups yielded common areas of activation in the supplementary motor area, precentral gyrus, and inferior frontal gyrus. aMCI patients also showed activation in the precuneus, temporal and postcentral gyri. Worse performance on the Stroop-fMRI task by the aMCI and mild AD groups suggests deficits in FA. This is the first study to investigate the neural correlates of FA using the Stroop task in aMCI and AD patients. The verbal Stroop-fMRI paradigm employed in the current study provides a means to study the neural correlates of FA in older adult and patient populations. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2009-12-31 11:57:52.374

Normal ageing is associated with decline in visual, cognitive, and physical functioning, with concurrent increases in the incidence of chronic medical conditions, including cognitive disorders. Determining when age-related changes have adversely affected a person’s ability to drive safely is a complex task, particularly when cognitive disorders such as mild cognitive impairment and dementia are present. The aim of this research was to assess the utility of a number of off-road measures in predicting Pass and Fail outcomes for older drivers on a blinded on-road driving assessment with a driving specialist occupational therapist and a driving instructor, which is considered the ‘gold standard’ measure of driving ability. The off-road measures included standardized cognitive tests, computerized sensory-motor & cognitive tests, medical conditions, and personality measures. The research project comprised three studies. In Study 1 (Healthy Older Drivers study), 60 drivers with no diagnosed cognitive disorder (‘cognitively-unimpaired’), aged 70-84 years (mean age 76.7, 50% male), completed standard cognitive tests, computerized sensory-motor and cognitive tests (SMCTests™), and measures of personality. Results were used to form classification models for on-road assessment Pass and Fail outcome. Sixteen participants failed the on-road assessment. A backwards stepwise binary logistic regression model selected a measure of executive function and a computerized measure of visuomotor planning and coordination as the best predictors. Following leave-one-out cross-validation, this model was estimated to correctly predict 60% of an independent group of cognitively-unimpaired older drivers into on-road Pass and Fail groups. In Study 2 (Healthy Driver Follow-up study), 56 participants from the Healthy Older Drivers study were followed for 24 months using annual telephone interviews to assess driving behaviour, driving attitudes, medical conditions, and the occurrence of crashes and receipt of traffic offences. Official data regarding crashes and traffic offences were also obtained. The aim was to determine whether either the on-road Pass/Fail classification or the off-road measures could predict subsequent crashes and offences. Failing the on-road assessment was not associated with higher crash or offence rates and there were only two baseline measures that predicted crashes or offences (i.e., distance driven at baseline testing and, paradoxically, a lower error score on a measure of visuomotor planning and coordination). However, drivers who reported more distress associated with their medical condition(s) were more likely to have had a crash or offence at 24 months. The outcomes of the Healthy Older Drivers and Healthy Driver Follow-up studies suggest that there is little value in off-road or on-road assessment of cognitively-unimpaired older drivers due to the weak relationship with future negative driving outcomes. However, distress associated with medical conditions may be a useful measure. Study 3 (Dementia and Driving study) recruited a sample of 60 driving assessment centre referrals with mild cognitive impairment or Alzheimer’s dementia. These participants, aged 58-92 years (mean age 77.9, 60% male), performed a computerized battery of sensory-motor and cognitive tests and a formal blinded on-road driving assessment. A backwards stepwise binary logistic regression model selected measures of reaction time and movement speed of the upper limbs, visuomotor planning and coordination, and sustained attention. Following leave-one-out cross-validation, this model was estimated to correctly predict 68% of an independent group of drivers with mild cognitive impairment and Alzheimer’s dementia into on-road Pass and Fail groups. A subsample of 32 participants completed additional standard cognitive tests and provided information on medical conditions. A binary logistic regression model in this subsample was formed which selected measures of verbal fluency, the presence of heart disease, and a comprehensive cognitive screen. Following leave-one-out crossvalidation, this model would be expected to correctly classify 75% of an independent group of drivers with mild cognitive impairment and Alzheimer’s dementia into on-road Pass and Fail groups. The three measures in this model could be performed in around 35-50 min in a primary health setting. It is concluded that off-road and on-road assessment of older drivers with no diagnosis of cognitive or neurological disorder is an inaccurate and inefficient use of driving assessment resources, both for the prediction of on-road driving performance and for predicting future crashes and traffic offences. The Dementia and Driving study found a model comprising three measures that could be performed in a primary health setting with reasonable accuracy for correctly classifying people with mild cognitive impairment and Alzheimer’s dementia who go on to Pass and Fail an on-road driving assessment.

Individuals with Parkinson’s disease (PD) often show cognitive impairments in addition to motor symptoms, with the majority of PD patients converting to dementia as the disease progresses. The changes in the microstructural integrity of key nodes in resting state networks (RSNs) could be a good indicator of the cognitive effects of PD on brain regions as it progresses to dementia. To assess the association between cognitive effects and microstructural change, the microstructural integrity of the regions of interest (ROIs) in 4 resting state networks (RSN), specifically the default mode network (DMN), based on DTI were obtained in three separate groups of patients with PD. One group of patients (PD-N) were cognitively normal, while the second group of patients (PD-MCI) reflect the transitional phase of mild cognitive impairment prior to dementia, and the third group of patients (PD-D) possessed a clear diagnosis of dementia. A comparison group of healthy controls (HC) were included, matched across the three patient groups. The PD-D group showed worse microstructural integrity for the majority of the ROIs across the 4 networks. The loss of structural integrity in the PD-MCI group was more selective, with some ROIs showing similar changes to PD-D, and others showing similar changes to the PD-N group. The PD-N group fail to show any changes in the structural integrity of any ROIs, relative to HC. For future study, a combined structural / functional study should be performed to examine if there are similar changes across both measures.

Parkinson’s disease (PD) is next to Alzheimer’s disease (AD) the second most common neurodegenerative disease. PD has traditionally been characterised as a motor disorder, but more recent research has revealed that cognitive impairments are frequent. Cognitive impairments in executive functions, attention, and working memory with reliance on dopaminergic transmission, are often described as dominating the cognitive profile in early-phase PD. However, although knowledge about the neuropathology that underlies the cognitive impairments in PD has increased, its features are complex and knowledge remains insufficient. Therefore, the aim of the current thesis was to improve the understanding of how task-evoked brain responses relate to cognitive status in patients with PD, with and without mild cognitive impairment (MCI), and to evaluate the predictive value of PD-MCI in respect of prodromal Parkinson’s disease dementia (PDD). This was conducted within the “new Parkinsonism in Umeå” (NYPUM) project, which is a prospective cohort study. Patients with idiopathic PD were included in this thesis, and the patients were examined with a comprehensive neuropsychological battery and with a functional MRI (fMRI) working memory protocol. During scanning, patients conducted a verbal two-back task in which they needed to maintain and actively update relevant information, and the primary outcome measure was blood-oxygen-level-dependent (BOLD) signal. This thesis shows that patients with PD-MCI had significantly lower BOLD signal responses than patients without MCI in frontal (anterior cingulate cortex) and striatal (right caudate) regions (Study I). The altered BOLD response in the right caudate was associated with altered presynaptic dopamine binding. The fronto-striatal alterations persisted across time but without any additional change. However, decreased posterior cortical (right fusiform gyrus) BOLD signal responses were observed in patients with PD-MCI relative to patients without MCI across time (Study II). Finally, PD-MCI at baseline examination is highly predictive for prodromal PDD with a six-fold increased risk. Cognitive tests with a posterior cortical basis, to a greater extent, are predictive for prodromal PDD than tests with a fronto-striatal basis. The observed working memory related alterations in patients with PD-MCI suggest that early cognitive impairments in PD are linked to fronto-striatal dopaminergic dysfunction. The longitudinal development of cognitive impairment in PD reflects additional posterior cortical dysfunction. This might reflect a dual syndrome, with dopamine-depleted fronto-striatal alterations that characterise PD-MCI in general, whereas additional posterior cortical cognitive alterations with a non-dopaminergic basis to a greater extent characterise prodromal PDD. If, and how, the two potential syndromes interact, is still unclear. Thus, this thesis provides information on cognitive neuropathological changes in PD that might contribute to more relevant choices of pharmacotherapy and diagnostic accuracy in respect of PDD. However, additional large-scale longitudinal imaging studies are needed to further clarify the neuropatholgogical features of PD-MCI in respect of prodromal PDD.

Amnestic mild cognitive impairment (aMCI) has been established as a significant risk factor for Alzheimer‟s disease (AD) and in many cases this state appears to represent an early or incipient stage of AD. Due to difficulties with the diagnosis and prognosis of aMCI and AD, as well as with the projected significant socioeconomic ramifications of AD, there is a need to establish sensitive and reliable biomarkers. The application of event related potentials (ERPs) has been recommended in this context due to their reliability, non-invasive nature, inexpense and relatively widespread availability. This thesis aims to further assess the potential efficacy of ERP markers for such applications. These aims are pursued via investigations of ERPs in healthy ageing, MCI and AD utilising an explicit recognition task that requires the use of key cognitive/memory processes which are often impaired in aMCI and AD. Two ERP effects were analysed: the N400effect which is assumed to index familiarity or trace strength, and the Late Positive Complex (LPC) which appears to index recollection or decision-related factors such as accuracy. Chapter 3 reports ERP and recognition accuracy comparisons between samples of 15 young (mean age = 21.73 years) and 15 older, cognitively healthy adults (mean age = 66.67 years). ERP data were acquired during performance of a word recognition task with high and low memory load conditions (long and short encoding lists, respectively). At test, participants were required to make old/new judgements to visually presented words. There was a trend for young participants to perform more accurately than the older sample, especially on the long list; although these differences only approached significance. However, the N400 old/new effect was found to be significantly reduced in the old compared with the young participants across memory load conditions. LPC old/new effects were generally not observed and this is likely due to the nature of the task which generally places minimal demands on controlled retrieval processes. These results indicate that the N400 effect may be more sensitive to the deleterious effects of ageing on recognition memory-related process(s) than behavioural measures of memory accuracy. Consistent with the view that the N400 indexes familiarity, these results are in accordance with other evidence that familiarity is affected in healthy ageing. The same methodology was used to compare ERPs between aMCI (n = 11) and healthy older adults (n = 11) in Chapter 4. The aMCI participants performed significantly worse than vi healthy elderly participants in discriminating „old‟ from „new‟ words. In the corresponding ERP data, healthy control sample demonstrated significant N400 old/new effects at parietal electrode locations, whereas aMCI participants failed to demonstrate significant N400 old/new effects at any electrode location. Again, LPC effects were not observed in either sample. The absence of significant N400 effects in aMCI participants may reflect a disruption of familiarity-based recognition in aMCI. These results converge with other evidence that the N400 effect may be a sensitive ERP marker useful for detecting, monitoring and/or predicting amnestic related cognitive decline. There are reported variations in underlying causes and sequelae of aMCI (e.g., not all progress to AD). Chapter 5 reports an exploratory investigation aimed at determining whether baseline ERPs differentiate between aMCI participants on the basis of their clinical diagnosis at follow-up. Baseline ERP data were compared in a small sample (n = 7) of aMCI participant who remained cognitively stable at 12-month follow-up (SMCI) with two aMCI participants who progressed to meet an AD diagnosis (PMCI) at the latter time-point. There was a trend for PMCI participants to display smaller old/new effects. However, only one participant displayed significantly smaller N400 old/new effects under low memory load conditions. Interestingly, this participant was also more impaired in baseline cognitive functioning. Chapter 6 examines the relationship between baseline ERPs and performance on neuropsychological assessment at 12-month follow-up in a sample of aMCI and AD participants (n =13) in order to investigate whether ERPs may prove informative for prognoses regarding general trajectories of cognitive decline, irrespective of diagnostic status. Smaller N400 old/new effects (at Fz and CPz) were associated with poorer performance on tasks assessing global cognitive functioning and auditory attention span. Reduced LPC old/new differences were related to poorer performance on tasks assessing global cognitive functioning, verbal learning and memory and better performance on a task assessing working memory at follow-up. In contrast to these results, no relationships were observed between ERP effects and concurrent performance on neuropsychological assessment in this sample, or in 42 elderly participants (including healthy, aMCI and AD), as described in Chapter 7. Taken together these results suggest that ERPs may be more sensitive in predicting future rather than concurrent cognitive functioning and may provide a more objective measure/classification of cognitive impairment vii irrespective of diagnosis. These outcomes are particularly novel as the relationship between baseline ERP data and follow-up neuropsychological measures does not appear to have been systematically reported in the literature to date. Collectively these findings indicate that ERP measure(s), particularly the N400 old/new effect, are sensitive to neurocognitive changes associated with ageing and aMCI, and may prove a useful biomarker for the early detection of AD. This is interesting as the effects of healthy ageing and pathological decline on the N400 from explicit recognition tasks have not been thoroughly explored. Moreover, the N400 (and perhaps, to a lesser degree, LPC) effect(s) appear to have substantial value for informing future prognoses of subsequent cognitive trajectories, at least for persons with amnestic impairment. These results may have significant clinical implications pertaining to the selection and application of efficacious therapeutic interventions in aMCI and AD.

This abstract will provide a brief overview of the following literature review. Alzheimer’s disease (AD) is the most common cause of dementia, and is a rapidly growing public health concern, as an increasing number of the world’s population is living well beyond 65 years of age. Alzheimer’s Disease is a progressive neurodegenerative condition, first presenting with mild memory impairment, and advancing over the course of years to profound memory loss, complete immobility, lack of speech and facial recognition. Currently, only palliative treatments are available to delay the progression of the disease, and lessen the severity of the cognitive impairment. However, until a cure is available, researchers and physicians have turned their attention to alternate therapies, one of the most important being exercise. Research efforts have now turned to examining the relationship between the positive physiological responses to exercise, and attenuation of the classic neurodegenerative patterns in patients with AD. The current study examined the effects of aerobic exercise, strength training and resistance-based exercise, and multimodal exercise (containing both of the aforementioned exercise modalities) on the physical and mental/cognitive health of patients with mild cognitive impairment (MCI) and AD. Thus far, exercise therapy has proven to be of great potential value as a supplement to pharmacological treatment, as well as a stand-alone prescription for patients with a milder form of cognitive impairment due to the onset of a neurodegenerative condition. The benefits can be grouped into two categories, cognitive and physiological. The effects on cognitive function range from improved memory to increased independence in activities of daily living, and the physiological effects range from improved clearance of amyloid beta plaques in the brain, to reduction of neuroinflammatory processes. The available research on this subject is extensive, covering a variety of exercise modalities at different intensities, and taking into consideration effects on individuals with MCI, early AD, and advanced AD. The general consensus is that continued, long-term adherence to an appropriate exercise routine can delay cognitive decline, and help patients with neurodegenerative diseases to live independently for a longer period of time. The improvements in cognition, memory, immediate recognition, and other related cognitive functions are mostly attributed to the heightened health of the brain tissue and neural circuitry due to exercise. Exercise (mainly aerobic) enhances cerebral blood flow, improves cardiovascular health, reduces the risk for type 2 diabetes mellitus, and has several other important effects that prevent the formation of pathological biomarkers of AD and promote neurogenesis. Atrophy of regions such as the hippocampus, amygdala, and cerebral cortex can be prevented, and reversed to a certain extent, as a result of long-term exercise therapy. The results of current research could assist physicians and caregivers to provide the appropriate type and intensity of exercise to patients with early, intermediate, and advanced stages of Alzheimer’s disease. Proactive exercise therapy for individuals with a known family history of neurodegenerative disease may help to maintain brain volume, specifically in the hippocampus, and reduce the risk of severe cognitive impairment. Future directions for research include examining the combined effects of pharmacological treatment and exercise therapy, and determining the average amount of time by which exercise delays the progression of early stage cognitive impairment to advanced impairment. Key Terms: aerobic exercise, Alzheimer’s disease, amyloid plaque, hippocampus, mild cognitive impairment, neurodegeneration, neurofibrillary tangle

abstract: ABSTRACT Millions of US aging individuals are at risk for mild cognitive impairment (MCI), the early stage of Alzheimer's disease (Ad). Ad is progressive; there is no clinical cure to date. Certain drugs treat symptoms yet fog memory. Memory activity is critical to strengthen cognition. The Phoenix Art Museum (PAM) and Banner Alzheimer's Institute (BAI) founded the Arts Engagement Program (AEP), a non-clinical, specialized arts program for adults with (MCI) and their caregiver. The museum environment is thought to enhance communication and raise self-esteem in certain MCI individuals. The interior surroundings may spurn memory enhancement. Scholarship to substantiate this theory is minimal; therefore, further studies are required. Empirical literature regarding design elements researched specific types of memory impairment was employed. The hypotheses that design elements of the museum's infrastructure and design elements from art themes enhance memory, and the results of these findings when applied to other environments enhance memory emerged. An experience-based study was performed. Semi-structured interviews noting design elements of both infrastructure and art were conducted after each of nine AEP sessions with volunteers from 8 dyads, a term used by the PAM as one caregiver and one MCI individual. The presiding docent was later interviewed. Volunteer interviews with dyads and docents was coded and ranked. Overlapping themes that tallied five or higher were considered significant due the low sample size. Results showed that neither group considered infrastructure design elements or art theme design elements a contributor to memory enhancement. The hypotheses proved null. Both groups expressed pleasure in experiencing the PAM’s environment. Keywords: MCI, infrastructure, art themes. / Dissertation/Thesis / Masters Thesis Design 2015

Objetivo: Avaliar a atrofia do corpo caloso (CC) em pacientes com doença de Alzheimer (DA) e comprometimento cognitivo leve (CCL) e quantificar quais regiões dessa estrutura são mais acometidas nessa doença como uso de técnicas quantitativas de ressonância magnética. Metodologia: O estudo contou com a participação de 75 indivíduos sendo 22 controles normais (CN), 30 com CCL e 23 com DA. O volume total do corpo caloso e suas 3 diferentes sub regiões foram delimitadas em cortes sagitais de imagem de ressonância magnética. Os volumes obtidos foram corrigidos para a variação de volume intracraniano. As mascaras foram co-registradas a mapas de relaxometria e transferência de magnetização para analise quantitativa. Resultados: Encontramos atrofia e redução dos valores de relaxometria e transferência de magnetização nos pacientes do grupo DA. As tres sub regiões do corpo caloso apresentaram redução de volume na doença sendo que a atrofia foi maior nas regiões anteriores. Não encontramos diferença significativa nos parâmetros estudados entre CCL e CN. Conclusões: Embora o corpo caloso esteja envolvido no processo de desconexão cortical presente na doença de Alzheimer seu envolvimento não é precoce. / Objective: To evaluate the atrophy of the corpus callosum (CC) in patients with Alzheimer disease (AD) and mild cognitive impairment (CCL) and quantify which regions of this structure are most affected in this disease as using quantitative MRI techniques. Methodology: The study counted on the participation of 75 individuals being 22 normal controls (CN), 30 with CCL and 23 with AI). The total volume of the corpus callosum and its v 3 different sub regions were delimited in sagittal sections of magnetic resonance imaging. The volumes obtained were corrected for intracranial volume variation. The masks were recorded with maps of relaxometry and transfer of magnetization for quantitative analysis. Results: We found atrophy and reduced values of relaxometry and magnetization transfer in patients in the AD group. The three sub regions of the corpus callosum showed volume reduction in the disease, with atrophy being greater in the anterior region. We found no significant difference in the parameters studied between CCL and CN fit .Conclusions: Although the corpus callosum is involved in the process of cortical detachment present in Alzheimer\'s disease, its involvement is late.

Introdução: Déficits de memória episódica constituem o marcador cognitivo mais frequente em pacientes com Comprometimento Cognitivo Leve (CCL).Estudos prévios mostram que déficits de memória episódica podem ser minimizados nestes pacientes por intervenções comportamentais. Entretanto, os mecanismos cerebrais envolvidos nos efeitos do treino cognitivo ainda são pouco explorados. O objetivo deste estudo foi avaliar o correlato neural por ressonância magnética funcional de um treino breve de memória em pacientes com CCL e compará-los com os achados em idosos saudáveis. Foram avaliados 18 pacientes com CCL e 19 idosos controles com a utilização de ressonância magnética funcional (RMf) em uma tarefa de codificação de listas de palavras com diferentes graus de relação semântica antes e após uma sessão de treino de estratégias de memória. Na sessão pré-treino, os participantes foram instruídos a memorizar as palavras durante a sessão de RMf sem qualquer orientação sobre o uso de estratégias de codificação. Após um treino breve no qual estratégias específicas de organização e agrupamento semântico foram exercitadas, os sujeitos foram reconduzidos ao aparelho de ressonância magnética e realizaram a sessão pós-treino, na qual foram instruídos a utilizar a estratégia treinada durante o paradigma de codificação de palavras. Os resultados dos exames de ressonância magnética funcional foram processados e analisados com o programa FSL versão 4.1. Ambos os grupos apresentaram aumento no número de palavras evocadas associado ao uso da estratégia treinada. Em ambos os grupos foi observado um aumento do sinal BOLD após o treino em regiões do córtex pré-frontal dorsolateral esquerdo e do córtex parietal bilateral. No grupo de idosos controles, entretanto, foi observada também uma redução da ativação em regiões do córtex parietal posterior esquerdo e cíngulo posterior bilateral, do córtex pré-frontal medial e cíngulo anterior direitos, do lóbulo parietal inferior e do córtex temporal superior direitos, do córtex pré-frontal dorsolateral direiro e do córtex óribito-frontal bilateral. A interação grupo x tempo foi significativa em áreas do córtex pré-frontal dorsolateral e ventromedial direitos. Estes resultado indicam que existem diferenças no recrutamento de regiões pré-frontais em resposta ao uso de estratégias de codificação em paradigmas de codificação de palavras entre pacientes com CCL e idosos cognitivamente saudáveis / The present studyinvestigated the effects of different applicationsof verbal learning strategies duringepisodicmemory encoding in patients with Mild Cognitive Impairment (MCI) (n=18) and normal controls (n=17) using functional magnetic resonance imaging (fMRI).The main goal of this study was to verify whether externally guided increases in verbal learning strategy application during episodic memory encoding modulate brain activity in memory-related networks in the same level in MCI as in controls. Participantswerescanned twice, using a word-list encoding fMRI paradigm.In the first session, self-initiated encoding strategies were used to intentionally memorize words during encoding. In the second session, participants received an explicit instruction to apply a semantic organization strategy (i.e. semantic clustering)to perform the task. The fMRI word list learning paradigm consisted of alternating blocks of encoding and resting baseline conditions. To perform the spontaneous fMRI session, participants were not instructed about the semantic organization of the words in the lists beforehand or given any practice with related lists. Therefore, any grouping by category observed in the subsequent free recall at the end of this fMRI acquisition was presumed to be self-initiated by the subject. At the end of the spontaneous session, each subject received a brief period of guidance or instructions to apply semantic strategies and organize words in terms of semantic categories during encoding, using a new set of word lists. Immediately after practicing the application of the strategy, participants were scanned again using the same type of paradigm as in the first session, except for the use of new set of word lists and the explicit instruction to apply semantic clustering.Free recall and strategic index scores were assessedafter each session. fMRI brain activation and deactivation during encoding of word lists in memory-related networks were examined across sessions. Results from the fMRI analysis revealed that after the explicit orientation to apply the verbal learning strategy, greater recruitment of frontoparietal network regions were observed in both MCI and control groups in relation to the unconstrained encoding condition. Group-differences in functional deactivations, however, were observed in the medial prefrontal (mPFC) cortex and in the right superior frontal gyrus, two critical nodes of the default mode network, related to the absence of modulation in the activity of the mPFC, along with a lack of suppression of the right superior frontal gyrus in MCI, in response to the increased use of the encoding strategy. A different association between improvement in strategy use and session-related changes in activation of the medial orbitalfrontal cortex between groups was also confirmed. That is, improvements in strategy use in controls contribute to a great extent in the amount of deactivation in OFC, whereas in patients, only a small portion of the increase in activation in this region was predicted by increases in strategy application